Pinealectomy ameliorates collagen II-induced arthritis in mice.

To extend our previous findings that exposure to constant darkness (stimulation of endogenous melatonin release) as well as treatment with exogenous melatonin magnifies the severity of collagen-induced arthritis in mice, we have examined the effects of melatonin cutback by removing the pineal gland. Two strains of mice, DBA/1 and NFR/N, were subjected to surgical pinealectomy. The melatonin levels in sera were reduced by approximately 70% by the pinealectomy compared with the corresponding sham-operated controls. After 3-4 weeks of rest the mice were immunized with rat type II collagen to induce autoimmune arthritis, and the animals were kept in constant darkness during the experiments. In comparison with the controls, all groups of pinealectomized mice showed reduced severity of the arthritis by means of (i) a slower onset of the disease, (ii) a less severe course of the disease (reduced clinical scores), and (iii) reduced serum levels of anti-collagen II antibodies. These effects were not significant in all experiments, but the trends were always the same. Thus, the present result strengthen the hypothesis that high physiological levels of melatonin (which can be induced by exposure to darkness) stimulate the immune system and cause exacerbation of autoimmune collagen II arthritis, while inhibition of melatonin release (pinealectomy or exposure to light) has a beneficial effect.